Functional Human Liver Cells Grown in the Lab

“This is the holy grail of liver research,” said Prof. Yaakov Nahmias.“Our technology will enable thousands of laboratories to study fatty liver disease, viral hepatitis, drug toxicit, and liver cancer at a fraction of the current cost.”

The international research team led by The Hebrew University of Jerusalem describes a new technique for growing human hepatocytes in the laboratory. This groundbreaking development could help advance a variety of liver-related research and applications, from studying drug toxicity to creating bio-artificial liver support for patients awaiting transplantations.

The liver is the largest internal organ in the human body, serving as the main site of metabolism. Human hepatocytes – cells that comprise 85% of the liver – are routinely used by the pharmaceutical industry for study of hepatotoxicity, drug clearance, and drug-drug interactions. They also have clinical applications in cell therapy to correct genetic defects, reverse cirrhosis, or support patients with a liver-assist device.

Regrettably, while the human liver can rapidly regenerate in vivo, recognized by the ancient Greeks in the myth of Prometheus, this capability to proliferate is rapidly lost when human cells are removed from the body. Thus far, attempts to expand human hepatocytes in the laboratory resulted in immortalized cancer cells with little metabolic function. The scarce supply of human hepatocytes and this inability to expand them without losing function is a major bottleneck for scientific, clinical, and pharmaceutical development.

To address this problem, Prof. Yaakov Nahmias, director of the Alexander Grass Center for Bioengineering at the Hebrew University of Jerusalem, partnered with leading German scientists at upcyte technologies GmbH (formerly Medicyte) to develop a new approach to rapidly expand the number of human liver cells in the laboratory without losing their unique metabolic function.

“The approach is revolutionary,” said Dr. Joris Braspenning, who led the German group. “Its strength lies in our ability to generate liver cells from multiple donors, enabling the study of patient-to-patient variability and idiosyncratic toxicity.” The team generated hepatocyte lines from ethnically diverse backgrounds that could be serially passaged, while maintaining CYP450 activity, epithelial polarization, and protein expression at the same level as primary human hepatocytes. Importantly, the proliferating hepatocytes showed identical toxicology response to primary human hepatocytes across 23 different drugs.

“This is the holy grail of liver research,” said Prof. Nahmias, the study’s lead author. “Our technology will enable thousands of laboratories to study fatty liver disease, viral hepatitis, drug toxicity and liver cancer at a fraction of the current cost.” Nahmias noted that genetic modifications preclude using the cells for transplantation, “but we may have found the perfect cell source for the bio-artificial liver project.”